Economic Evaluations of Chimeric Antigen Receptor T-Cell Therapies for Hematologic and Solid Malignancies: A Systematic Review.

OBJECTIVES: This study aimed to systematically review evidence on the cost-effectiveness of chimeric antigen receptor T-cell (CAR-T) therapies for patients with cancer. METHODS: Electronic databases were searched in October 2022 and updated in September 2023. Systematic reviews, health technology assessments, and economic evaluations that compared costs and effects of CAR-T therapy in patients with cancer were included. Two reviewers independently screened studies, extracted data, synthesized results, and critically appraised studies using the Philips checklist. Cost data were presented in 2022 US dollars. RESULTS: Our search yielded 1809 records, 47 of which were included. Most of included studies were cost-utility analysis, published between 2018 and 2023, and conducted in the United States. Tisagenlecleucel, axicabtagene ciloleucel, idecabtagene vicleucel, ciltacabtagene autoleucel, lisocabtagene maraleucel, brexucabtagene autoleucel, and relmacabtagene autoleucel were compared with various standard of care chemotherapies. The incremental cost-effectiveness ratio (ICER) for CAR-T therapies ranged from $9424 to $4 124 105 per quality-adjusted life-year (QALY) in adults and from $20 784 to $243 177 per QALY in pediatric patients. Incremental cost-effectiveness ratios were found to improve over longer time horizons or when an earlier cure point was assumed. Most studies failed to meet the Philips checklist due to a lack of head-to-head comparisons and uncertainty surrounding CAR-T costs and curative effects. CONCLUSIONS: CAR-T therapies were more expensive and generated more QALYs than comparators, but their cost-effectiveness was uncertain and dependent on patient population, cancer type, and model assumptions. This highlights the need for more nuanced economic evaluations and continued research to better understand the value of CAR-T therapies in diverse patient populations.

Associations of preoperative anaemia with healthcare resource use and outcomes after colorectal surgery: a population-based cohort study.

BACKGROUND: Preoperative anaemia is common in patient undergoing colorectal surgery. Understanding the population-level costs of preoperative anaemia will inform development and evaluation of anaemia management at health system levels. METHODS: This was a population-based cohort study using linked, routinely collected data, including residents from Ontario, Canada, aged ≥18 yr who underwent an elective colorectal resection between 2012 and 2022. Primary exposure was preoperative anaemia (haemoglobin <130 g L-1 in males; <120 g L-1 in females). Primary outcome was 30-day costs in 2022 Canadian dollars (CAD), from the perspective of a publicly funded healthcare system. Secondary outcomes included red blood cell transfusion, major adverse events (MAEs), length of stay (LOS), days alive at home (DAH), and readmissions. RESULTS: We included 54,286 patients, with mean 65.3 (range 18-102) years of age and 49.0% females, among which 21 264 (39.2%) had preoperative anaemia. There was an absolute adjusted cost increase of $2671 per person at 30 days after surgery attributable to preoperative anaemia (ratio of means [RoM] 1.05, 95% confidence interval [CI] 1.04-1.06). Compared with the control group, 30-day risks of transfusion (odds ratio [OR] 4.34, 95% CI 4.04-4.66), MAEs (OR 1.14, 95% CI 1.03-1.27), LOS (RoM 1.08, 95% CI 1.07-1.10), and readmissions (OR 1.16, 95% CI 1.08-1.24) were higher in the anaemia group, with reduced DAH (RoM 0.95, 95% CI 0.95-0.96). CONCLUSIONS: Approximately $2671 CAD per person in 30-day health system costs are attributable to preoperative anaemia after colorectal surgery in Ontario, Canada.

Incremental net monetary benefit of using varenicline for smoking cessation: A systematic review and meta-analysis of economic evaluation studies.

AIMS: To conduct a systematic review and meta-analysis and pool the incremental net benefits (INBs) of varenicline compared with behaviour support with bupropion or nicotine replacement therapy (NRT), behaviour support alone and unaided cessation in adult smokers making a first-time attempt to quit. METHODS: A search for economic evaluation studies was conducted from inception to 30 September 2022, on PubMed, Embase, Cost-Effectiveness Analysis (CEA) Registry by Tufts Medical Centre, EconLit and the NHS Economic Evaluation Database (NHS EED). Eligible studies were included if they were (1) conducted among adults ages 18 years old and older who were smokers attempting to quit for the first time; (2) compared varenicline to behaviour support with bupropion or NRT, behaviour support alone and unaided cessation; and (3) performed a CEA or cost-utility analysis. The INBs were calculated and pooled across studies stratified by country income level and study perspective using the random-effects model. Statistical heterogeneity between studies was assessed using the I2 statistic and Cochrane Q statistic. RESULTS: Of the 1433 identified studies, 18 studies were included in our review. Our findings from healthcare system/payer perspective suggested that the use of varenicline is statistically significantly cost-effective compared with bupropion (pooled INB, $830.75 [95% confidence interval, $208.23, $1453.28]), NRTs ($636.16 [$192.48, $1079.84]) and unaided cessation ($4212.35 [$1755.79, $6668.92]) in high-income countries. Similarly, varenicline is also found to be cost-effective compared to bupropion ($2706.27 [$1284.44, $4128.11]), NRTs ($3310.01 [$1781.53, $4838.50]) and behavioural support alone ($5438.22 [$4105.99, $6770.46]) in low- and middle-income countries. CONCLUSION: Varenicline is cost-effective as a smoking cessation aid when compared with behavioural support with bupropion or nicotine replacement therapies and behavioural support alone in both high-income countries and low- and middle-income countries, from the healthcare system/payer perspective in adult smokers who attempt to quit for the first time.

Protocol for the ONLOOP trial: pragmatic randomized trial evaluating a province-wide system of personalized reminders for evidence-based surveillance tests in adult survivors of childhood cancer in Ontario.

BACKGROUND: Childhood cancer treatment while often curative, leads to elevated risks of morbidity and mortality. Survivors require lifelong periodic surveillance for late effects of treatment, yet adherence to guideline-recommended tests is suboptimal. We created ONLOOP to provide adult survivors of childhood cancer with detailed health information, including summaries of their childhood cancer treatment and recommended surveillance tests for early detection of cardiomyopathy, breast cancer, and/or colorectal cancer, with personalized reminders over time. METHODS: This is an individually randomized, registry-based pragmatic trial with an embedded process and economic evaluation to understand ONLOOP's impact and whether it can be readily implemented at scale. All adult survivors of childhood cancer in Ontario overdue for guideline-recommended tests will be randomly assigned to one of two arms: (1) intervention or (2) delayed intervention. A letter of information and invitation will detail the ONLOOP program. Those who sign up will receive a personalized toolkit and a screening reminder 6 months later. With the participants' consent, ONLOOP will also send their primary care clinician a letter detailing the recommended tests and a reminder 6 months later. The primary outcome will be the proportion of survivors who complete one or more of the guideline-recommended cardiac, breast, or colon surveillance tests during the 12 months after randomization. Data will be obtained from administrative databases. The intent-to-treat principle will be followed. Based on our analyses of administrative data, we anticipate allocating at least 862 individuals to each trial arm, providing 90% power to detect an absolute increase of 6% in targeted surveillance tests completed. We will interview childhood cancer survivors and family physicians in an embedded process evaluation to examine why and how ONLOOP achieved success or failed. A cost-effectiveness evaluation will be performed. DISCUSSION: The results of this study will determine if ONLOOP is effective at helping adult survivors of childhood cancer complete their recommended surveillance tests. This study will also inform ongoing provincial programs for this high-risk population. TRIAL REGISTRATION: ClinicalTrials.gov NCT05832138.

Resource Use and Costs of Indwelling Pleural Catheters vs Pleurodesis for Malignant Pleural Effusions: A Population-based Study.

RATIONALE: Malignant pleural effusions (MPE) are associated with significant health service use and healthcare costs, but the current evidence is limited. OBJECTIVES: To compare 12-month post-procedure: (1) health service utilization, and (2) healthcare costs following indwelling pleural catheter (IPC) insertion with at-home drainage performed by homecare nursing services, versus in-hospital chemical pleurodesis. METHODS: We performed a retrospective population-based study on a cohort of adults with MPE who underwent IPC insertion or chemical pleurodesis between January 1, 2015 and December 31, 2019 using provincial health administrative data (Ontario, Canada). Patients were followed from the procedure date until death or until 12-month post-procedure. Inverse probability of treatment weighting (IPTW) was performed to adjust for imbalances in baseline characteristics. Differences in length of stay (LOS), readmissions, emergency department visits, home care visits, and healthcare costs were estimated using weighted regression analysis. RESULTS: Of 5,752 included individuals, 4432 (77%) underwent IPC insertion and 1320 (23%) had pleurodesis. In the weighted sample, individuals who received an IPC had fewer inpatient days (12.4 days vs 16 days, standardized mean difference 0.229), but a higher proportion of subsequent admissions for empyema (2.7% vs 1.1%, p=0.0002) compared to those undergoing pleurodesis. IPC individuals received more hours of nursing home care (41 hours vs 21.1 hours, standardized mean difference 0.671) but overall had lower average healthcare costs ($40,179 vs $46,640 per patient, standardized mean difference 0.177) than those receiving pleurodesis. CONCLUSIONS: IPCs with home nursing drainage are associated with reduced health resource use compared to pleurodesis in adults with MPE even after controlling for important baseline and clinical characteristics. Given that both procedures have similar health outcomes, our findings support the ongoing promotion of IPCs to increase outpatient management of patients with MPEs. Primary source of funding: TOHAMO Innovation Fund grant.

Economic evaluation of non-invasive liver tests for the diagnosis of liver fibrosis in chronic liver diseases: a systematic review protocol.

OBJECTIVE: The objective of this review is to determine the costs and benefits of non-invasive liver tests vs liver biopsy in patients with chronic liver diseases. INTRODUCTION: Hepatic diseases can lead to liver fibrosis, cirrhosis, and hepatocellular carcinoma. In the past, liver biopsy was the only option for diagnosing fibrosis degree. Liver biopsy is an invasive procedure that depends on the sample size to be able to deliver an accurate diagnosis. In recent years, non-invasive liver tests have been increasingly used to estimate liver fibrosis degree; however, there is a lack of economic assessments of technology implementation outcomes. INCLUSION CRITERIA: This review will include partial (cost studies) and complete economic evaluation studies on hepatitis B, hepatitis C, alcoholic liver disease, and non-alcoholic fatty liver disease that compare non-invasive liver tests with liver biopsies. Studies published in English, French, Spanish, German, Italian, or Portuguese will be included. No date limits will be applied to the search. METHODS: This review will identify published and unpublished studies. Published studies will be identified using MEDLINE (PubMed), Cochrane Library (CENTRAL), Embase, Web of Science, Scopus, and LILACS. Sources of unpublished studies and gray literature will include sources from health technology assessment agencies, clinical practice guidelines, regulatory approvals, advisories and warnings, and clinical trial registries, as well as Google Scholar. Two independent reviewers will screen and assess studies, and extract and critically appraise the data. Data extracted from the included studies will be analyzed and summarized to address the review objective using narrative text, and the JBI dominance ranking matrix. REVIEW REGISTRATION: PROSPERO CRD42023404278.

Cost-effectiveness of postoperative imaging surveillance strategies for nonfunctional pituitary adenomas after resection with curative intent.

OBJECTIVE: The aim of this study was to determine an optimal follow-up imaging surveillance strategy in terms of cost-effectiveness after resection of nonfunctioning pituitary adenomas with curative intent. METHODS: An individual-level state-transition microsimulation model was used to simulate costs and outcomes associated with three postoperative imaging strategies over a lifetime time horizon: 1) annual MRI surveillance, 2) tapered MRI surveillance (annual surveillance for 5 years followed by surveillance every 2 years), and 3) personalized surveillance (annual surveillance for 5 years followed by surveillance every 2 years when MRI shows remnant disease/postoperative changes, and surveillance at 7, 10, and 15 years for disease-free MRI). Transition probabilities, utilities, and costs were estimated from recent published data and discounted by 3% annually. Model outcomes included lifetime costs (2022 US dollars), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). RESULTS: Under base case assumptions, annual surveillance yielded higher costs and lower health effects (QALYs) compared with the tapered and personalized surveillance strategies (dominated). Personalized surveillance demonstrated an additional 0.1 QALY at additional cost ($1298) compared with tapered surveillance (7.7 QALYs at a cost of $12,862). The ICER was $11,793/QALY. The optimal decision was most sensitive to the probability of postoperative changes on MRI after surgery and MRI cost. Accounting for parameter uncertainty, personalized surveillance had a higher probability of being a cost-effective surveillance option compared with the alternative strategies at 79%. CONCLUSIONS: Using standard cost-effectiveness thresholds in the US ($100,000/QALY), personalized surveillance that accounted for remnant disease or postoperative changes on MRI was cost-effective compared with alternative surveillance strategies.

A cost-effectiveness analysis of national smoking cessation services among chronic obstructive pulmonary disease patients in Thailand.

AIMS: Thailand's national smoking cessation services (FAH-SAI clinics) were founded in 2010. A cost-effectiveness analysis (CEA) is needed to inform policymakers of the allocation and prioritization of the limited budget to maximize the value for money of reimbursing these services. Chronic obstructive pulmonary disease (COPD) patients would benefit from smoking cessation services. Therefore, this study aimed to assess the cost-effectiveness of these multidisciplinary services compared to the usual care among COPD patients in Thailand from a societal perspective. METHODS: We conducted a CEA from a societal perspective using a Markov model to simulate lifetime costs and quality-adjusted life years (QALYs) gained by each smoking cessation intervention over the patient's lifetime. We derived the effectiveness of the smoking cessation services from a multicenter, longitudinal study of smoking cessation services in Thailand and estimated the natural quit rate, transition probabilities, health utility, and cost data from the published literature. Costs and outcomes were discounted at 3%. Sensitivity analyses were performed. RESULTS: Compared to the usual care, FAH-SAI clinics were associated with higher costs (4,207 THB (US$133)) and improved QALYs (0.11), with an incremental cost-effectiveness ratio of 37,675 THB/QALY (US$1,187/QALY). The effectiveness of FAH-SAI clinics was a key driver of the cost-effectiveness results. At the willingness-to-pay (WTP) threshold of 160,000 THB (US$5,042) per QALY gained, the probability of being cost-effective was 96.5%. CONCLUSIONS: FAH-SAI clinics were cost-effective under Thailand's WTP threshold. Our results could inform policymakers in allocating resources to support smoking cessation services for COPD patients in Thailand.

Index hospital cost of adverse events following thoracic surgery: a systematic review of economic literature.

OBJECTIVES: Adverse events (AEs) following thoracic surgery place considerable strain on healthcare systems. A rigorous evaluation of the economic impact of thoracic surgical AEs remains lacking and is required to understand the value of money of formal quality improvement initiatives. Our objective was to conduct a systematic review of all available literature focused on specific cost of postoperative AEs following thoracic surgery. DESIGN: Systematic review of the economic literature was performed, following recommendations from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. DATA SOURCES: An economic search filter developed by the Canadian Agency for Drugs and Technologies in Health was applied, and MEDLINE, Embase and The Cochrane Library were searched from inception to January 2022. ELIGIBILITY CRITERIA: We included English articles involving adult patients who underwent a thoracic surgical procedure with estimated costs of postoperative complications. Eligible study designs included comparative observational studies, randomised control trials, decision analytic or cost-prediction models, cost analyses, cost or burden of illness studies, economic evaluation studies and systematic reviews and/or meta-analyses of cost analyses and cost of illness studies. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened titles and abstracts in the first stage and full-text articles of included studies in the second stage. Disagreements during abstract and full-text screening stages were resolved via discussion until a consensus was reached. Studies were appraised for methodological quality using the Critical Appraisal Skills Program checklist. RESULTS: 3349 studies were identified: 20 met inclusion criteria. Most were conducted in the USA (12/20), evaluating AE impact on hospital expenditures (18/20). 68 procedure-specific AE mean costs were characterised (USD$). The most commonly described were anastomotic leak (mean:range) (USD$49 278:$6 176-$133 002) and pneumonia ($12 258:$2608-$34 591) following esophagectomy, and prolonged air leak ($2556:$571-$3573), respiratory failure ($19 062:$11 841-$37 812), empyema ($30 189:$23 784-$36 595), pneumonia ($15 362:$2542-$28 183), recurrent laryngeal nerve injury ($16 420:$4224-$28 616) and arrhythmia ($6835:$5833-$8659) following lobectomy. CONCLUSIONS: Hospital costs associated with AEs following thoracic surgery are substantial and varied. Quantifying costs of AEs enable future economic evaluation studies, which could help prioritising value-directed quality improvement to optimally improve outcomes and reduce costs.

Can routinely collected administrative data effectively be used to evaluate and validate endpoints used in breast cancer clinical trials? Protocol for a scoping review of the literature.

BACKGROUND: Randomized controlled trials (RCTs) are a critical component of evidence-based medicine and the evolution of patient care. However, the costs of conducting a RCT can be prohibitive. A promising approach toward reduction of costs and lessening of the burden of intensive and lengthy patient follow-up is the use of routinely collected healthcare data (RCHD), commonly called real-world data. We propose a scoping review to identify existing RCHD case definitions of breast cancer progression and survival and their diagnostic performance. METHODS: We will search MEDLINE, EMBASE, and CINAHL to identify primary studies of women with either early-stage or metastatic breast cancer, managed with established therapies, that evaluated the diagnostic accuracy of one or more RCHD-based case definitions or algorithms of disease progression (i.e., recurrence, progression-free survival, disease-free survival, or invasive disease-free survival) or survival (i.e., breast-cancer-free survival or overall survival) compared with a reference standard measure (e.g., chart review or a clinical trial dataset). Study characteristics and descriptions of algorithms will be extracted along with measures of the diagnostic accuracy of each algorithm (e.g., sensitivity, specificity, positive predictive value, negative predictive value), which will be summarized both descriptively and in structured figures/tables. DISCUSSION: Findings from this scoping review will be clinically meaningful for breast cancer researchers globally. Identification of feasible and accurate strategies to measure patient-important outcomes will potentially reduce RCT budgets as well as lessen the burden of intensive trial follow-up on patients. SYSTEMATIC REVIEW REGISTRATION: Open Science Framework ( https://doi.org/10.17605/OSF.IO/6D9RS ).

Clustering of Health Behaviors in Canadians: A Multiple Behavior Analysis of Data from the Canadian Longitudinal Study on Aging.

BACKGROUND: Health behaviors such as physical inactivity, unhealthy eating, smoking tobacco, and alcohol use are each leading risk factors for non-communicable chronic disease. Better understanding which behaviors tend to co-occur (i.e., cluster together) and co-vary (i.e., are correlated) may provide novel opportunities to develop more comprehensive interventions to promote multiple health behavior change. However, whether co-occurrence or co-variation-based approaches are better suited for this task remains relatively unknown. PURPOSE: To compare the utility of co-occurrence vs. co-variation-based approaches for understanding the interconnectedness between multiple health-impacting behaviors. METHODS: Using baseline and follow-up data (N = 40,268) from the Canadian Longitudinal Study of Aging, we examined the co-occurrence and co-variation of health behaviors. We used cluster analysis to group individuals based on their behavioral tendencies across multiple behaviors and to examine how these clusters are associated with demographic characteristics and health indicators. We compared outputs from cluster analysis to behavioral correlations and compared regression analyses of clusters and individual behaviors predicting future health outcomes. RESULTS: Seven clusters were identified, with clusters differentiated by six of the seven health behaviors included in the analysis. Sociodemographic characteristics varied across several clusters. Correlations between behaviors were generally small. In regression analyses individual behaviors accounted for more variance in health outcomes than clusters. CONCLUSIONS: Co-occurrence-based approaches may be more suitable for identifying sub-groups for intervention targeting while co-variation approaches are more suitable for building an understanding of the relationships between health behaviors.

Health behaviors such as physical inactivity, unhealthy eating, smoking tobacco, and alcohol use are each leading risk factors for non-communicable chronic disease. A better understanding of which behavioral combinations people engage in, and which behaviors are associated with each other, may provide new insights to support the development of interventions to promote multiple health behavior change. Using data with two time points (N = 40,268) from the Canadian Longitudinal Study of Aging, we grouped people into clusters based on their health behaviors and examined how these clusters are associated with demographic characteristics and health indicators. Seven clusters were identified with sociodemographic patterns evident across several clusters. Correlations between behaviors were generally small. We compared whether individual health behaviors, or groupings of people based on their health behaviors, were better predictors of future health outcomes. Individual behaviors were slightly better predictors of future health outcomes than clusters.

Cost-effectiveness analysis of the SMART quit clinic program in smokers with cardiovascular disease in Thailand.

INTRODUCTION: The SMART Quit Clinic Program (FAHSAI Clinic) has been implemented in Thailand since 2010; however, it remains unclear whether the benefits gained from this program justify its costs. We assessed its cost-effectiveness compared to usual care in a population of Thai smokers with cardiovascular disease (CVD) from a societal perspective. METHODS: We conducted a cost-utility analysis using a Markov model to simulate lifetime costs and quality-adjusted life years (QALYs) of Thai smokers aged ≥35 years receiving smoking cessation services offered from FAHSAI Clinic or usual care over a horizon of 50 years. The model used a 6-month continuous abstinence rate from a multicenter prospective study of 24 FAHSAI Clinics. A series of sensitivity analyses including probabilistic sensitivity analysis were conducted to assess robustness of study findings. Cost data are presented in US$ for 2020. RESULTS: The FAHSAI Clinic was dominant as it was less costly ($9537.92 vs $10964.19) and more effective (6.06 vs 5.96 QALYs) compared with usual care over the 50-year time horizon. Changes in risks of stroke and coronary heart disease among males had the largest impact on the cost-effectiveness findings. The probability that FAHSAI Clinic was cost-effective was 99.8% at a willingness-to-pay threshold of $5120. CONCLUSIONS: The FAHSAI Clinic smoking cessation program was clinically superior and cost-saving compared to usual care for Thai patients with CVD in all scenarios. A budget impact analysis is needed to estimate the financial impact of adopting this program within the Thai healthcare system.

FLUID trial: a hospital-wide open-label cluster cross-over pragmatic comparative effectiveness randomised pilot trial comparing normal saline to Ringer's lactate.

OBJECTIVES: Normal saline (NS) and Ringer's lactate (RL) are the most common crystalloids used for fluid therapy. Despite evidence of possible harm associated with NS (eg, hyperchloremic metabolic acidosis, impaired kidney function and death), few large multi-centre randomised trials have evaluated the effect of these fluids on clinically important outcomes. We conducted a pilot trial to explore the feasibility of a large trial powered for clinically important outcomes. DESIGN: FLUID was a pragmatic pilot cluster randomised cross-over trial. SETTING: Four hospitals in the province of Ontario, Canada PARTICIPANTS: All hospitalised adult and paediatric patients with an incident admission to the hospital over the course of each study period. INTERVENTIONS: A hospital wide policy/strategy which stocked either NS or RL throughout the hospital for 12 weeks before crossing over to the alternate fluid for the subsequent 12 weeks. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary feasibility outcome was study fluid protocol adherence. Secondary feasibility outcomes included time to Research Ethics Board (REB) approval and trial initiation. Primary (composite of death or re-admission to hospital in first 90 days of index hospitalisation) and secondary clinical outcomes were analysed descriptively. RESULTS: Among 24 905 included patients, mean age 59.1 (SD 20.5); 13 977 (56.1%) were female and 21 150 (85.0%) had medical or surgical admitting diagnoses. Overall, 96 821 L were administered in the NS arm, and 78 348 L in the RL arm. Study fluid adherence to NS and RL was 93.7% (site range: 91.6%-98.0%) and 79.8% (site range: 72.5%-83.9%), respectively. Time to REB approval ranged from 2 to 48 days and readiness for trial initiation from 51 to 331 days. 5544 (22.3%) patients died or required hospital re-admission in the first 90 days. CONCLUSIONS: The future large trial is feasible. Anticipating and addressing logistical challenges during the planning stages will be imperative. TRIAL REGISTRATION NUMBER: NCT02721485.

Impacts of medical and non-medical cannabis on the health of older adults: Findings from a scoping review of the literature.

BACKGROUND: Cannabis legalization has enabled increased consumption in older adults. Age-related mental, physical, and physiological changes may lead to differences in effects of cannabis in older adults compared to younger individuals. OBJECTIVE: To perform a scoping review to map the evidence regarding the health effects of cannabis use for medical and non-medical purposes in older adults. METHODS: Electronic databases (MEDLINE, Embase, PsycINFO, Cochrane Library) were searched for systematic reviews (SRs), randomized controlled trials (RCTs) and non-randomized/observational studies (NRSs) assessing the health effects and associations of cannabis use (medical or non-medical) in adults ≥ 50 years of age. Included studies met age-related inclusion criteria or involved a priori identified health conditions common among older adults. Records were screened using a liberal accelerated approach and data charting was performed independently by two reviewers. Descriptive summaries, structured tables, effect direction plots and bubble plots were used to synthesize study findings. FINDINGS: From 31,393 citations, 133 publications describing 134 unique studies (26 SRs, 36 RCTs, 72 NRSs) were included. Medical cannabis had inconsistent therapeutic effects in specific patient conditions (e.g., end-stage cancer, dementia), with a number of studies suggesting possible benefits while others found no benefit. For medical cannabis, harmful associations outnumbered beneficial, and RCTs reported more negative effects than NRSs. Cannabis use was associated with greater frequencies of depression, anxiety, cognitive impairment, substance use and problematic substance use, accidents/injuries, and acute healthcare use. Studies often were small, did not consistently assess harms, and did not adjust for confounding. DISCUSSION: The effects of medical cannabis are inconsistent within specific patient conditions. For older adults, generally, the available evidence suggests cannabis use may be associated with greater frequencies of mental health issues, substance use, and acute healthcare use, and the benefit-to-risk ratio is unclear. Studies with a balanced assessment of benefits and harms may guide appropriate public health messaging to balance the marketing pressures of cannabis to older adults.

Assessment of the real-world impact of the Thai smoking cessation programme on clinical outcomes: protocol for a multicentre prospective observational study.

BACKGROUND: Tobacco smoking is the most common preventable cause of morbidity and mortality in the world. In an effort to counteract the harmful consequences of smoking, various tobacco control measures have been implemented, including the use of smoking cessation programmes to reduce the number of new smokers as well as helping current smokers to quit smoking. In Thailand, the SMART Quit Clinic Program (FAH-SAI Clinics) was launched in 2010 to provide smoking cessation services by a multidisciplinary team. There are currently 552 FAH-SAI Clinics established across all 77 provinces of Thailand. AIM: This protocol describes a study aiming to evaluate the SMART Quit Clinic Program (FAH-SAI Clinics) in terms of programme performance and clinical outcomes. We hope that the results of the study could be used to improve the current service model and the programme's success. METHOD: A multicentre prospective observational study will be conducted. The study will focus on 24 FAH-SAI Clinics across 21 provinces of Thailand. The primary outcomes are seven-day point prevalence abstinence rate and continuous abstinence rate at three and six months. The outcomes will be measured using a self-reported questionnaire and biochemical validated by exhaled carbon monoxide. DISCUSSION: This study will be the first real-world study that reports the effectiveness of the well-established smoking cessation programme in Thailand. Findings from this study can help improve the quality of smoking cessation services provided by multidisciplinary teams and other smoking cessation services, especially those implemented in low- and middle-income countries.

Interventions to address potentially inappropriate prescriptions and over-the-counter medication use among adults 65 years and older in primary care settings: protocol for a systematic review.

PURPOSE: To inform recommendations by the Canadian Task Force on Preventive Health Care on potentially inappropriate prescribing and over-the-counter (OTC) medication use among adults aged 65 years and older in primary care settings. This protocol outlines the planned scope and methods for a systematic review of the benefits and harms and acceptability of interventions to reduce potentially inappropriate prescriptions and OTC medication use. METHODS: De novo systematic reviews will be conducted to synthesize the available evidence on (a) the benefits and harms of interventions to reduce potentially inappropriate prescriptions and OTC medications compared to no intervention, usual care, or non- or minimally active intervention among adults aged 65 years and older and (b) the acceptability of these interventions or attributes among patients. Outcomes of interest for the benefits and harms review are all-cause mortality, hospitalization, non-serious adverse drug reactions, quality of life, emergency department visits, injurious falls, medical visits, and the number of medications (and number of pills). Outcomes for the acceptability review are the preference for and relative importance of different interventions or their attributes. For the benefits and harms review, we will search MEDLINE, Embase, and Cochrane Central Register of Controlled Trials for randomized controlled trials. For the acceptability review, we will search MEDLINE, Embase, PsycInfo, Cochrane Central Register of Controlled Trials, and the NHS Economic Evaluation Database for experimental and observational studies with a comparator. Websites of relevant organizations, other grey literature sources, and reference lists of included studies and reviews will be searched. Title and abstract screening will be completed by two independent reviewers using the liberal accelerated approach. Full-text review, data extraction, risk of bias assessments, and GRADE (Grading of Recommendations Assessment, Development and Evaluation) will be completed independently by two reviewers, with any disagreements resolved by consensus or by consulting with a third reviewer. The GRADE approach will be used to assess the certainty of the evidence for outcomes. DISCUSSION: The results of this systematic review will be used by the Canadian Task Force on Preventive Health Care to inform their recommendation on potentially inappropriate prescribing and OTC medication use among adults aged 65 years and older. SYSTEMATIC REVIEW REGISTRATION: PROSPERO (KQ1: CRD42022302313; KQ2: CRD42022302324); Open Science Framework ( https://osf.io/urj4b/ ).

Engaging Patients and Caregivers in an Early Health Economic Evaluation: Discerning Treatment Value Based on Lived Experience.

BACKGROUND: Traditionally, economic evaluations have engaged clinicians and policymakers; however, patients and their caregivers have insight that can ensure that the economic evaluation process appropriately reflects disease consequences and adequately addresses their priorities related to treatment. OBJECTIVE: We aimed to identify patient priorities to inform an early economic evaluation of chimeric antigen receptor T-cell therapy for adults with relapsed or refractory B-cell acute lymphoblastic leukemia. METHODS: We conducted two online group discussions of four participants each, involving patients with experience of hematological cancer and a caregiver. We used an adapted version of the nominal group technique, a consensus-building discussion approach, to generate focused qualitative data. RESULTS: Patients and a caregiver acknowledged both the costs directly related to clinical care, such as the out-of-pocket cost of drugs, and the indirect treatment costs, such as the cost of transport, accommodation, and food. The emotional and physical toll of treatment and the influence of treatment on employment and education were additional costs emphasized by participants. Treatment benefits prioritized by participants included the efficacy of treatment, manageable side effects, improved quality of life, accessibility of treatment, and short treatment duration. CONCLUSIONS: Engaging patients and caregivers in an early economic evaluation could help identify additional costs and benefits of therapies that are not typically recognized in economic evaluations but have the potential to increase the commercial viability of novel therapies. This research also demonstrates how patients and caregivers can be engaged at different levels in the development of early economic evaluation models.

The Impact of Virtual Cancer Care on Chemotherapy Delivery and Clinical Outcomes in Colorectal Cancer Patients Receiving Systemic Therapy: A Pre- and Intra-Pandemic Analysis.

(1) Background: The coronavirus 2019 pandemic has resulted in an abrupt transition to virtual oncology care worldwide. This study's objective is to evaluate chemotherapy delivery and clinical outcomes in patients on systemic treatment for colorectal cancer before and during the pandemic. (2) Methods: Clinical data was collected on patients with colorectal cancer receiving intravenous chemotherapy at The Ottawa Hospital from June 2019 to March 2021. Patients were stratified by whether they were started on chemotherapy pre-pandemic (June 2019-January 2020) or intra-pandemic (February 2020-March 2021). Multiple regression analysis was used to compare outcomes between pandemic periods; (3) Results: There were 220 patients included in this study. The proportion of virtual consultations (1.2% to 64.4%) and follow-up visits (5.2% to 83.3%) increased during the pandemic. There was no difference in the incidence of treatment delays (OR = 1.01, p = 0.78), chemotherapy dose reductions (OR = 0.99, p = 0.69), emergency department visits (OR = 1.23, p = 0.37) or hospitalizations (OR = 0.73, p = 0.43) between pandemic periods. A subgroup analysis revealed no difference in outcomes independent of the presence of metastases; (4) Conclusion: These findings serve as an important quality-care indicator and demonstrate that virtual oncology care appears safe in a cohort of high-risk colorectal cancer patients.

The impact of Thai multidisciplinary smoking cessation program on clinical outcomes: A multicentre prospective observational study.

Introduction: Tobacco use is the leading preventable cause of morbidity and mortality worldwide. Since 2010, Thailand has implemented a multidisciplinary smoking cessation clinic, which provides smoking cessation services, but the effectiveness of the clinics was not formally evaluated. This study was conducted to assess the real-world effectiveness of this multidisciplinary smoking cessation program. Methods: We conducted a prospective, multicentre, observational study on Thai participants aged 13 years and older in 24 smoking cessation clinics across Thailand's 13 health regions. Each clinic offered smoking cessation interventions according to the well-established 5As model for smoking cessation (Ask, Advise, Assess, Assist, and Arrange). Outcomes of interest were continuous abstinence rates (CAR) at 3 and 6 months. Biochemical confirmation and self-reporting were used to assess the outcomes. Descriptive statistics (mean, SD, median, IQR, and percentage) were used to analyze the smoking cessation outcomes in both intention-to-treat and per-protocol analysis approaches. Results: Smokers receiving services from the Thai multidisciplinary smoking cessation clinics had CAR of 17.49 and 8.33% at 3 and 6 months, respectively. For those with cardiovascular disease (CVD) or cerebrovascular disease, CAR was found to be 26.36% at 3 months and 13.81% at 6 months. While participants with chronic obstructive pulmonary disease (COPD) had CAR ranging from 32.69% at 3 months to 17.31% at 6 months. Conclusion: The multidisciplinary team smoking cessation clinic was effective in assisting smokers in quitting smoking. The effectiveness of the clinic was more pronounced for smokers with CVD, cerebrovascular disease, or COPD. Findings from this study support a decision to include multidisciplinary smoking cessation clinics in the universal health care benefits package.

Cost-effectiveness of direct surgery versus preoperative octreotide therapy for growth-hormone secreting pituitary adenomas.

PURPOSE: The objective of this study was to compare the cost-effectiveness of preoperative octreotide therapy followed by surgery versus the standard treatment modality for growth-hormone secreting pituitary adenomas, direct surgery (that is, surgery without preoperative treatment) from a public third-party payer perspective. METHODS: We developed an individual-level state-transition microsimulation model to simulate costs and outcomes associated with preoperative octreotide therapy followed by surgery and direct surgery for patients with growth-hormone secreting pituitary adenomas. Transition probabilities, utilities, and costs were estimated from recent published data and discounted by 3% annually over a lifetime time horizon. Model outcomes included lifetime costs [2020 United States (US) Dollars], quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). RESULTS: Under base case assumptions, direct surgery was found to be the dominant strategy as it yielded lower costs and greater health effects (QALYs) compared to preoperative octreotide strategy in the second-order Monte Carlo microsimulation. The ICER was most sensitive to probability of remission following primary therapy and duration of preoperative octreotide therapy. Accounting for joint parameter uncertainty, direct surgery had a higher probability of demonstrating a cost-effective profile compared to preoperative octreotide treatment at 77% compared to 23%, respectively. CONCLUSIONS: Using standard benchmarks for cost-effectiveness in the US ($100,000/QALY), preoperative octreotide therapy followed by surgery may not be cost-effective compared to direct surgery for patients with growth-hormone secreting pituitary adenomas but the result is highly sensitive to initial treatment failure and duration of preoperative treatment.